Identification of pendrin as a common mediator for mucus production in bronchial asthma and chronic obstructive pulmonary disease

Isao Nakao, Sachiko Kanaji, Shoichiro Ohta, Hidetomo Matsushita, Kazuhiko Arima, Noriko Yuyama, Mutsuo Yamaya, Katsutoshi Nakayama, Hiroshi Kubo, Mika Watanabe, Hironori Sagara, Kumiya Sugiyama, Hiroyuki Tanaka, Shuji Toda, Hiroaki Hayashi, Hiromasa Inoue, Tomoaki Hoshino, Aya Shiraki, Makoto Inoue, Koichi SuzukiHisamichi Aizawa, Satoshi Okinami, Hiroichi Nagai, Mamoru Hasegawa, Takeshi Fukuda, Eric D. Green, Kenji Izuhara

Research output: Contribution to journalArticlepeer-review

98 Citations (Scopus)

Abstract

Excessive production of airway mucus is a cardinal feature of bronchial asthma and chronic obstructive pulmonary disease (COPD) and contributes to morbidity and mortality in these diseases. IL-13, a Th2-type cytokine, is a central mediator in the pathogenesis of bronchial asthma, including mucus overproduction. Using a genome-wide search for genes induced in airway epithelial cells in response to IL-13, we identified pendrin encoded by the SLC26A4 (PDS) gene as a molecule responsible for airway mucus production. In both asthma and COPD mouse models, pendrin was up-regulated at the apical side of airway epithelial cells in association with mucus overproduction. Pendrin induced expression of MUC5AC, a major product of mucus in asthma and COPD, in airway epithelial cells. Finally, the enforced expression of pendrin in airway epithelial cells in vivo, using a Sendai virus vector, rapidly induced mucus overproduction in the lumens of the lungs together with neutrophilic infiltration in mice. These findings collectively suggest that pendrin can induce mucus production in airway epithelial cells and may be a therapeutic target candidate for bronchial asthma and COPD.

Original languageEnglish
Pages (from-to)6262-6269
Number of pages8
JournalJournal of Immunology
Volume180
Issue number9
DOIs
Publication statusPublished - 2008 May 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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